Comparative evaluation of three commercial Toxoplasma-specific IgG antibody avidity tests and significance in different clinical settings.
ABSTRACT Determination of the avidity of specific IgG antibodies has become a generally accepted diagnostic aid for dating Toxoplasma infection. In this study, the Labsystems, VIDAS and EUROIMMUN Toxoplasma IgG avidity assays were compared on a series of 133 Toxoplasma IgG- and IgM-positive sera from symptomatic patients (n=28), from pregnant (n=43) and non-pregnant (n=26) women, and on 18 IgG-positive and IgM-negative sera from chronically infected patients. The results showed excellent concordance between the Labsystems and VIDAS tests in both the IgM-positive (r=0.82, kappa=0.771) and IgM-negative (kappa=0.609) sera, whilst the agreement of the EUROIMMUN assay with both the Labsystems and VIDAS tests in the IgM-positive sera was moderate (kappa=0.575 and kappa=0.525, respectively) and in the IgM-negative sera was poor (kappa=0.000). Analysis of the kinetics of the maturation of avidity in 13 patients in whom follow-up sera were available showed that, despite a general trend of maturation, in two patients the avidity did not become high during 6 and 11 months of follow-up. In view of the clinical setting, in the symptomatic patients, despite one case of complete discrepancy and five cases of partial discrepancy, the Labsystems and VIDAS tests were in almost perfect agreement (kappa=0.812), whilst the agreement in pregnant and non-pregnant women was substantial (kappa=0.754 and kappa=0.708, respectively). In conclusion, the Labsystems and VIDAS tests are equally reliable for the measurement of Toxoplasma IgG avidity; the choice of test should depend on the laboratory set-up. The EUROIMMUN test may be an acceptable alternative in resource-limited settings, but should be used prudently.
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ABSTRACT: Antibody avidity, defined as the strength of binding between antibody and antigen, represents a functional measure of affinity maturation of antibodies. Determination of the antibody avidity is usually performed separating high and low avidity antibodies by dissociating agents, but measurement of the antibody avidity in humans is rather complicated, due to the heterogeneity of the antibodies produced in response to complex antigens, e.g. after vaccinations. The purpose of the present study was to evaluate the experimental determinants of the assessment of avidities of IgG antibodies directed against pertussis toxin (IgG-anti-PT) and filamentous hemagglutinin (IgG-anti-FHA) produced after pertussis vaccination using an adapted ELISA and ammonium thiocyanate (NH(4)SCN) as dissociating agent. Our experiments revealed that the results of avidity testing depend very much on experimental conditions and may over- or underestimate the relative avidity of IgG-anti-PT and IgG-anti-FHA antibodies. Whereas in our findings avidity seems to be independent from the initial antibody concentration in a wide range of measures, RAI depends on NH(4)SCN concentration, time of incubation and temperature of the reaction. The presented method allows an accurate measurement of the IgG antibody avidity against both Bordetella pertussis antigens PT and FHA, using NH(4)SCN as chaotropic agent in concentrations lower than 3.0M for 20min time of incubation at 37°C. Different experimental conditions in testing pertussis-specific IgG antibody avidity should be considered in interpretation and comparability of data of different studies.Journal of immunological methods 09/2012; · 2.35 Impact Factor
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ABSTRACT: Toxoplasma infection in pregnant women may cause congenital toxoplasmosis. Diagnosis of infection is based on serological tests aimed at detecting IgM and IgG antibodies against Toxoplasma gondii. However, IgM antibodies are not an accurate marker for discriminating between acute and latent infection. Detection of residual or persistent IgM may occur months or even years after primary infection, while the IgG avidity test is a rapid means for identifying latent infections in pregnant women who exhibit both IgG and IgM anti-Toxoplasma antibodies on initial testing during pregnancy. In this study, we assessed and compared the performance of four commercially available Toxoplasma IgG avidity tests in immunocompetent and immunocompromised patients with acute and latent toxoplasmosis. Positive predictive value of high avidity to confirm latent toxoplasmosis was 100% for all the assays indicating that high avidity is a hallmark of latent infection. However, negative predictive value of high avidity ranged from 99.2% (bioMérieux) to 95.3% (Abbott) indicating that that acute toxoplasmosis could not be reliably diagnosed based on low IgG avidity alone. Thus, the avidity test provides a rapid means for identifying latent Toxoplasma infection in immunocompetent pregnant women presenting both IgG and IgM anti-Toxoplasma antibodies on initial testing. In terms of cost-effectiveness, avidity testing is a powerful tool that optimizes screening and follow-up of pregnant women while it minimizes the costs of screening by avoiding subsequent costly maternal and fetal investigation and unnecessary treatment. The cheapest assay, VIDAS® Toxo IgG Avidity, also had the best performance for the diagnosis of latent toxoplasmosis.Clinical and vaccine Immunology: CVI 12/2012; · 2.60 Impact Factor
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ABSTRACT: Toxocariasis is a helminth zoonosis caused by infection with the larvae of Toxocara spp. ascarid worms. Only two species, Toxocara canis and Toxocara cati, are recognised as causative agents of human disease. The best choice for serodiagnosis of the generalised forms of toxocariasis, visceral larva migrans (VLM) or covert toxocariasis, relies upon the initial use of TES-ELISA, after which any positive result should subsequently be tested by Western blotting (WB). Covert toxocariasis is mostly a benign infection, so a large majority of infected subjects are asymptomatic or have very few symptoms and therefore go undiagnosed. In this form, this helminthosis is often self-limiting, leaving residual specific antibodies. A positive serodiagnosis caused by residual antibodies that do not have any diagnostic significance can be associated with any infectious or non-infectious disease. If separated from the ongoing clinical and laboratory context, such a positive result has no diagnostic value and should be only taken into account after the possible etiologies of any observed syndromes have been ruled out. Unlike the methods used for the immunodiagnosis of bacterial, viral or protozoal (toxoplasmosis) infections, it is not possible with toxocariasis to assess the age of the presence of specific IgG using the levels of specific IgM because IgM antibodies can be found throughout the course of helminthiasis. The detection of other classes of immunoglobulins, namely IgE and IgA, the subclasses, namely IgG4 or circulating Ag was proven to be unable to discriminate between active and self-cured generalised toxocaral infections. Currently, the diagnosis of an active covert toxocariasis relies upon indirect arguments, e.g., the presence of otherwise unexplained symptoms along with blood eosinophilia and/or elevated levels of eosinophil cationic protein (ECP). This situation is far from ideal and more research should be carried out to solve this difficult problem.Veterinary Parasitology 12/2012; · 2.38 Impact Factor